REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE)

Leveraging access to the blood supply and blood donors, the REDS-IV-P program began conducting the RESPONSE study (REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic) in early 2020 in order to 1) evaluate if SARS-CoV-2 RNA was found in blood donations in the U.S. using an assay that could potentially be used to screen the blood supply if evidence of SARS-CoV-2 transfusion-transmission became apparent 2) conduct serosurveys using optimized assays/algorithms to monitor antibody reactivity in blood donor populations over time, 3) enroll SARS-CoV-2 positive donors and others into a longitudinal cohort study to answer fundamental questions about the evolution of viremia and immune responses, and 4) establish a sharable biorepository that includes specimens collected early on in the infection and potentially large volumes of plasma from infected/convalescent donors.<br>

Screening for SARS-CoV-2 RNAemia was completed using a SARS-CoV-2 nucleic acid test (NAT) performed on retained blood donor minipool samples from six geographic regions in the US. The study also included serosurveillance (i.e. testing for antibody directed against the SARS-CoV2 spike protein) of donations from the same six regions to document accruing seroincidence in blood donor populations and to project these rates in the general population. To enrich for donors with acute SARS-CoV-2 infection, another part of the study focused on donors reporting post-donation information (PDI) consistent with COVID-19 by testing plasma from all available PDI donations for SARS-CoV-2 RNA by NAT. Subjects who were diagnosed with COVID-19 based on PDI reports or who tested positive by SARS-CoV-2 NAT on index donation plasma were enrolled into a longitudinal follow-up study which collected multiple samples for up to one-year post-infection. The longitudinal follow-up study also enrolled community members who reported a new positive SARS-CoV-2 NAT test in the prior 7-14 days.

The specific aims of the RESPONSE study were to:
1. Establish the incidence of SARS-CoV-2 RNAemia in blood donations from the American Red Cross (ARC) regions in Los Angeles, Boston, and Minneapolis metropolitan areas, Bloodworks Northwest (BWNW), New York Blood Center (NYBC), and Vitalant San Francisco Bay Area, monthly between March and September of 2020 1. Conduct serosurveys to study antibody reactivity in same six areas as above monthly for March to August 2020 1. Document rates of Post Donation Information (PDI) reports to determine PDI rates relevant to SARS-CoV-2 clinical disease and test index donation plasma from PDI donors for SARS-CoV-2 RNA 1. Enroll SARS-CoV-2 infected subjects into a longitudinal cohort study to answer fundamental questions on the evolution of viremia, early immune responses and waning of immunity over 3-12 months of follow-up 1. Establish a sharable biorepository of samples from all of the above Aims for future research
The data from Aims 3 and 4 above is being made available in BioData Catalyst.

Biospecimens for these Aims are managed by Vitalant Research Institute (VRI). More information on [biospecimens](https://biolincc.nhlbi.nih.gov/studies/reds_iv_response/) is available.

凭借对血液供应系统及献血者资源的获取渠道，REDS-IV-P项目于2020年初启动了RESPONSE研究（REDS-IV-P新型SARS-CoV-2疫情流行病学、监测与防范研究），旨在：1）采用一种检测方法评估美国献血样本中是否存在SARS-CoV-2 RNA——若出现SARS-CoV-2输血传播证据，该方法或可用于血液供应筛查；2）通过优化的检测方法/算法开展血清学调查，长期监测献血人群的抗体反应性；3）招募SARS-CoV-2阳性献血者及其他人群加入纵向队列研究，解答关于病毒血症演变和免疫应答的基础问题；4）建立可共享的生物样本库，收录感染早期采集的标本及可能来自感染者/康复者的大量血浆。

SARS-CoV-2 RNA血症筛查通过对留存的献血者迷你池样本进行SARS-CoV-2核酸检测（NAT）完成。该研究还包括对上述六个地区献血样本的血清学调查（即检测针对SARS-CoV-2刺突蛋白的抗体），以记录献血人群的血清学发病率并推算普通人群的发病率。为富集急性SARS-CoV-2感染的献血者，研究的另一部分聚焦于报告献血后信息（PDI）且符合COVID-19特征的献血者，通过NAT检测其所有可用PDI献血样本中的SARS-CoV-2 RNA。基于PDI报告被诊断为COVID-19的受试者，或首次献血血浆中SARS-CoV-2 NAT检测呈阳性的受试者，被纳入纵向随访研究——该研究在感染后长达一年内采集多个样本。纵向随访研究还招募了过去7-14天内报告SARS-CoV-2 NAT检测新阳性的社区成员。

RESPONSE研究的具体目标为：1. 确定2020年3月至9月期间，美国红十字会（ARC）洛杉矶、波士顿及明尼阿波利斯大都会地区、西北血液中心（BWNW）、纽约血液中心（NYBC）和维塔兰特旧金山湾区中心献血样本中SARS-CoV-2 RNA血症的月度发病率；1. 于2020年3月至8月期间，每月在上述六个地区开展血清学调查，研究抗体反应性；1. 记录献血后信息（PDI）报告率，以确定与SARS-CoV-2临床疾病相关的PDI率，并检测PDI献血者首次献血血浆中的SARS-CoV-2 RNA；1. 招募SARS-CoV-2感染受试者加入纵向队列研究，解答关于病毒血症演变、早期免疫应答及3-12个月随访期间免疫衰减现象的基础问题；1. 建立包含上述所有目标样本的可共享生物样本库，以供未来研究使用。上述目标3和4的数据已在BioData Catalyst平台开放获取。

这些目标所需的生物标本由维塔兰特研究所（VRI）管理。有关生物标本的更多信息可查阅[生物标本](https://biolincc.nhlbi.nih.gov/studies/reds_iv_response/)。